Validation of an Assay to Measure Cyclooxygenase-1 Activity
| Status: | Completed |
|---|---|
| Conditions: | Healthy Studies |
| Therapuetic Areas: | Other |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 10/14/2017 |
| Start Date: | May 2007 |
| End Date: | January 2010 |
Validation of an Ex Vivo Cyclooxygenase-1 Catalytic Assay in Humans
The purpose of this study is to obtain a reference range for a newly developed assay of ex
vivo platelet COX-1 activity in normal volunteers taking a routine clinical dose of aspirin.
vivo platelet COX-1 activity in normal volunteers taking a routine clinical dose of aspirin.
Aspirin has been shown to reduce cardiovascular events in at-risk individuals, but some
aspirin-treated patients fail to exhibit expected changes in bleeding time and platelet
aggregation. Recent evidence has correlated aspirin "non-response" to poor cardiovascular
outcomes.
In order to study the mechanisms of aspirin resistance, an assay is needed to measure the
catalytic activity of platelet cyclooxygenase (which should be inhibited by aspirin). A
common assay in general use is the measurement of thromboxane B2 production in clotting whole
blood. This measure, however, is influenced by genetic and environmental variations in the
glass-activated coagulation pathway, albumin binding capacity, platelet activation pathways,
arachidonic acid pools, and phospholipase activity.
Our laboratory has developed a direct assay of platelet cyclooxygenase (COX-1) activity that
is not influenced by these variations. This study will generate a reference range in normal
volunteers taking a routine clinical dose of aspirin (81mg daily) for this assay. In
addition, by using two aspirin formulations (enteric-coated and chewable), the study design
additionally allows the secondary comparison of the effects of these two formulations on
COX-1 inhibition.
aspirin-treated patients fail to exhibit expected changes in bleeding time and platelet
aggregation. Recent evidence has correlated aspirin "non-response" to poor cardiovascular
outcomes.
In order to study the mechanisms of aspirin resistance, an assay is needed to measure the
catalytic activity of platelet cyclooxygenase (which should be inhibited by aspirin). A
common assay in general use is the measurement of thromboxane B2 production in clotting whole
blood. This measure, however, is influenced by genetic and environmental variations in the
glass-activated coagulation pathway, albumin binding capacity, platelet activation pathways,
arachidonic acid pools, and phospholipase activity.
Our laboratory has developed a direct assay of platelet cyclooxygenase (COX-1) activity that
is not influenced by these variations. This study will generate a reference range in normal
volunteers taking a routine clinical dose of aspirin (81mg daily) for this assay. In
addition, by using two aspirin formulations (enteric-coated and chewable), the study design
additionally allows the secondary comparison of the effects of these two formulations on
COX-1 inhibition.
Inclusion Criteria:
- Non-smoker
- No chronic medical illness
- No chronic medications
Exclusion Criteria:
- Aspirin/NSAID use in preceding 14 days
- History of chronic NSAID use
- Currently taking NSAIDs, opioid analgesics, corticosteroids, or anticoagulants
- History of coronary artery disease, myocardial infarction, coronary artery bypass
grafting, percutaneous angioplasty, diabetes mellitus, or stroke.
- History of hypertension
- Body mass index > 35
- History of gastric, duodenal, or esophageal ulcers or serious gastrointestinal bleed
- History of frequent headaches, pain syndrome, or other condition requiring frequent
use of analgesics
- History of adverse reactions to aspirin
- Screening platelet count < 100,000/ul or > 500,000/ul
- Screening hematocrit < 35% or > 50%
- Weight less than 110 pounds
- Pregnant females
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